The genus Ranunculus L. (Ranunculus) in Asia: a review of its botany, traditional uses, phytochemistry, pharmacology, toxicity, and pharmaceutical preparations.

OBJECTIVES: Ranunculus L. genus contains 413 species, and it is the biggest genus in the family Ranunculaceae Juss. This review is to provide botanical characteristics, traditional uses, phytochemistry, pharmacology, toxicity, and pharmaceutical preparations of the genus Ranunculus. KEY FINDINGS: The genus Ranunculus contains flavonoids, organic acids, coumarins, lactones, glycosides, sterols, polysaccharides, and trace elements. These chemical constituents complement the pharmacological actions and work together to exert anti-inflammatory, anticancer, antitubercular, antibacterial, antimalarial, etc. Those traditional Chinese medicine characteristics, like clearing away heat and detoxification, make this genus significant in ethnic medicine. The progress in research and the development of various pharmaceutical preparations made it appear in epidemiological and clinical studies. SUMMARY: The genus Ranunculus has attracted the attention of experts and scholars in many fields due to its unique advantages. However, there are many species that are not scientifically investigated. The toxicity issues are also a huge concern. Fortunately, the toxicity can be overcome via special processes like drying or heating and by choosing a safe extraction solvent, such as water thus ensuring the safety of medication. Pharmaceutical preparations containing the plants from Ranunculus have gratifying clinical value, but they are not promoted sufficiently. Therefore, further research should be carried out to promote the genus for its health benefits to humans.

ß-Escin: An Updated Review of Its Analysis, Pharmacology, Pharmacokinetics, and Toxicity.

[Formula: see text]-Escin is an oleanane-type pentacyclic triterpenoid saponin extracted from the seeds of Aesculus hippocastanum (AH), which is more widely distributed. [Formula: see text]-Escin sodium has been approved by the American FDA for clinical usage. This paper is intended to summarize an updated and comprehensive review of the pharmacological activities, pharmacokinetic properties, toxicity, and analytical methods of [Formula: see text]-escin. Studies have shown that [Formula: see text]-escin has significant antitumor, antiviral, anti-inflammatory, and other activities alongside less adverse effects and higher safety than other compounds. The review shows that the pharmacological effects of [Formula: see text]-escin involve mechanisms such as ATM/[Formula: see text]H2AX, RhoA/Rock, GSK-3[Formula: see text]/[Formula: see text]-Catenin, HER2/HER3/Akt, and PI3K/Akt signaling pathways, and Cyclin A, p21[Formula: see text], survivin, Bcl-2, Mcl-1, Caspases, TGF-[Formula: see text], MMPs, and TNF-[Formula: see text] among other inflammatory factors. [Formula: see text]-Escin has significant cytotoxicity; the use of the chitosan/xanthan gum-based polyelectrolyte complexes PA1 and PC-11 to modify it not only to reduces its toxicity, but also improves its drug efficacy. Because of this, these compounds may become a new research hotspot. [Formula: see text]-Escin in vivo metabolism can be converted by the CYP1A2 enzyme in the intestinal flora to produce [Formula: see text]-escin, deacylated, deglycosylated, and 21[Formula: see text]-[Formula: see text]-crotonoyl-protoescin, and the binding rate of the plasma proteins is higher than 90%. These are mainly metabolized by the liver, kidneys, and other organs, and excreted in the form of urine and feces. The number of reports on the specific mediators of the metabolism of [Formula: see text]-escin and their mechanisms and metabolites is relatively small; furthermore, the results are vague. Therefore, a complete and in-depth exploration of the pharmacokinetic characteristics of [Formula: see text]-escin is needed to provide a more complete and effective theoretical reference for the study of its pharmacodynamic activity.

Bryum billardieri Schwaegr. against EV71 infection: in vitro and in vivo antiviral effects, identification of molecular mechanisms and active monomers.

Enterovirus 71 (EV71) commonly causes symptoms such as hand, foot, and mouth disease (HFMD) in infants and children and may lead to neurological disease and even death in severe cases. Appropriate vaccines for the prevention of HFMD are available in the clinic; however, they present different and serious adverse effects that cannot guarantee compliance and efficacy. The purpose of this study was to analyze the potential mechanism of Bryum billardieri Schwaegr. (BBS) against EV71 and analyze its potential active components. A previous in vitro antiviral assay was used to determine the best extraction method for the active site of BBS against EV71, and the results showed that the antiviral activity of BBS was more pronounced in the fraction that was extracted by aqueous extraction and alcoholic precipitation and then obtained by purification on a silica gel column (dichloromethane:methanol = 0:100). In addition, the therapeutic effects of BBS on EV71-infected mice were further investigated by in vivo pharmacological experiments. BBS reduced the lung index, viral titer, and degree of EV71-induced lung, brain, and skeletal muscle damage. The mechanism of anti-EV71 activity of BBS was also investigated by using ELISA and qRT-PCR, and it was found that BBS exerted its action mainly by regulating the expression of TLR3, TLR4, TNF-α, IL-2, and IFN-γ by modulating the activation of NF-κB and JAK2/STAT1 signaling pathways. Finally, the chemical structures of the active monomers in BBS were determined by using UPLC-MS and NMR techniques. The study revealed that one of the monomers on which BBS exerts its antiviral activity is saponarin. In conclusion, the results of this study suggest that BBS is considered a natural anti-EV71 product with enormous potential, and saponarin would be its non-negligible active monomer.

Antiviral Activity against Respiratory Syncytial Virus of Polysaccharide from Jerusalem Artichoke (Helianthus tuberosus L.).

Jerusalem artichoke (Helianthus tuberosus L.) polysaccharide (JAP) is a chain polysaccharide composed of D-fructose connected by ß (1-2) glycosidic bonds, which is a kind of inulin. This study evaluated the anti-respiratory syncytial virus (RSV) activity of JAP in vivo and in vitro. To investigate its antiviral activity, an MTT assay, q-PCR, enzyme-linked immunosorbent assay (ELISA), and lung histological observation were performed. The results showed that JAP showed anti-RSV activity in vitro with a half maximal inhibitory concentration (IC50) of approximately 29.15 µg/mL. In vivo results suggested that JAP could effectively inhibit RSV proliferation in the lungs and improve lung tissue lesions in RSV-infected mice. Additionally, JAP could also reduce the expression of TLR3 and TLR4 in the lungs, increase serum anti-inflammatory factors IL-4 levels, and reduce pro-inflammatory factors TNF-α and TNF-ß levels, which may be related to its anti-RSV activity. This study provides a new approach to anti-RSV therapy and enriches the potential applications of JAP.

[Chemical constituents and pharmacological effects of Dictamni Cortex: a review].

Dictamni Cortex, the dried root bark of Dictamnus dasycarpus, has many chemical constituents, such as alkaloids, limonoids, flavonoids, sesquiterpenoids, glycosides, and steroids.It has the effects of anti-inflammation, anti-fungi, anti-arteriosclerosis, stopping bleeding, anti-cancer, neuroprotection, and antioxidation.The chemical constituents of Dictamni Cortex are the important material basis for its medicinal effects.This paper reviewed the chemical constituents and pharmacological activities of Dictamni Cortex and analyzed the research trend and present research progress on this medicinal, with a view to its further development and utilization.

Hyperoside: A review on its sources, biological activities, and molecular mechanisms.

Hyperoside is a natural flavonol glycoside in various plants, such as Crataegus pinnatifida Bge, Forsythia suspensa, and Cuscuta chinensis Lam. Medical research has found that hyperoside possesses a broad spectrum of biological activities, including anticancer, anti-inflammatory, antibacterial, antiviral, antidepressant, and organ protective effects. These pharmacological properties lay the foundation for its use in treating multiple diseases, such as sepsis, arthritis, colitis, diabetic nephropathy, myocardial ischemia-reperfusion, pulmonary fibrosis, and cancers. Hyperoside is obtained from the plants and chemical synthesis. This study aims to provide a comprehensive overview of hyperoside on its sources and biological activities to provide insights into its therapeutic potential, and to provide a basis for high-quality studies to determine the clinical efficacy of this compound.

Sophoridine: A review of its pharmacology, pharmacokinetics and toxicity.

BACKGROUND: Sophoridine is a bioactive alkaloid found in many Chinese herbs, such as Sophora alopecuroides l, Euchresta japonica Benth and Sophora moocrorftinan. Sophoridine hydrochloride injection has been approved as an anticancer drug in China. PURPOSE: This review aims to provide a comprehensive summary on the pharmacological, molecular mechanism, pharmacokinetic and toxicity studies of sophoridine. METHOD: PubMed, Web of Science and China National Knowledge Infrastructure were used for a systematic search with the keywords including "sophoridine", "pharmacology", "pharmacokinetics", and "toxicity". RESULTS: Emerging evidence suggests that sophoridine exhibits a broad spectrum of pharmacological activities including antitumor, anti-inflammatory, antiviral, myocardialprotective and hepatoprotective activities. These pharmacological properties lay foundation for using the plants containing sophoridine for the treatment of numerous diseases, such as cancer, colitis, injury of lungs, ischemia myocardial,etc. The mechanisms involved in the pharmacological actions of sophoridine are regulation of NF-κB, TLR4/IRF3, JNK/ERK, Akt/mTOR signaling pathways, down-regulating the expression of HMG3B, bcl-2, MMP-2, MMP-9, TNF-α, IL-1ß IL-6 and other cytokines or kinases. However, an increasing number of published reports indicated that sophoridine has serious adverse effects. The primary toxic effects are neurotoxicity and acute toxicity, which are of wide concern in worldwide. Moreover, sophoridine is reported to distribute in kidney, liver, uterus, lung and other organs. It undergoes glucuronidation and excreted in urine. CONCLUSION: Future studies should elucidate the detailed in vivo metabolism studies on sophoridine. The effect of substituent functional groups on sophoridine on metabolism, the enzymes involved in the metabolism and the chemistry of metabolites also should be studied. Either structural modification of sophoridine or its combined with other drugs may play a pivotal role to enhance its pharmacological activities and reduce its toxicity.

Fructus arctii: an overview on its traditional uses, pharmacology and phytochemistry.

OBJECTIVES: Fructus arctii (F. arctii) is the dried ripe fruit of Arctium lappa Willd (Asteraceae). It is being used as a traditional medicine in China, Japan, Iran, Europe, Afghanistan, India, etc. for cough, inflammation, clearing the heat, detoxification, cancer and diabetes. This review summarized the botanical description, distribution, ethnopharmacology, bioactive constituents and pharmacological actions of F. arctii including methods to assess its quality. In addition, this review also provides insights into future research directions on F. arctii to further explore its bioactive constituents, mechanism involved in pharmacological activity, and clinical use including the development of new analytical methods for assessing the quality. KEY FINDINGS: The comprehensive analysis of the literature revealed that F. arctii contains lignans, volatile oil, flavonoids, sesquiterpenoids, triterpenes, phenolic acids, etc. Experimental studies on various extracts and drug formulations showed that it has antioxidant, antimicrobial, hypoglycaemic, lipid-lowering, anti-inflammatory, analgesic, antiviral, anti-tumour activity, etc. SUMMARY: The pharmacological activity of a few major constituents in F. arctii have been identified. However, there are still need more studies and more new technologies to prove the pharmacological activity and the effective mechanism of the other constituents that undergoing uncertain. Except for the animal experiments, clinical studies should be carried out to provide the evidence for clinical application.

Polysaccharides derived from Chinese medicinal herbs: A promising choice of vaccine adjuvants.

Adjuvants have been used in vaccines for a long time to promote the body's immune response, reducing vaccine dosage and production costs. Although many vaccine adjuvants are developed, the use in human vaccines is limited because of either limited action or side effects. Therefore, the development of new vaccine adjuvants is required. Many studies have found that natural polysaccharides derived from Traditional Chinese medicine (TCM) possess good immune promoting effects and simultaneously improve humoral, cellular and mucosal immunity. Recently polysaccharide adjuvants have attracted much attention in vaccine preparation because of their intrinsic characteristics: immunomodulation, biocompatibility, biodegradability, low toxicity and safety. This review article systematically analysed the literature on polysaccharides possessing vaccine adjuvant activity from TCM plants, such as Astragalus polysaccharide (APS), Rehmannia glutinosa polysaccharide (RGP), Isatis indigotica root polysaccharides (IRPS), etc. and their derivatives. We believe that polysaccharide adjuvants can be used to prepare the vaccines for clinical use provided their mechanisms of action are studied in detail.

Chamomile: A Review of Its Traditional Uses, Chemical Constituents, Pharmacological Activities and Quality Control Studies.

Matricaria chamomilla L. (MC) and Chamaemelum nobile (L.) All. (CN) are two varieties of Chamomile. These herbs have been used for thousands of years in Greece, Rome and ancient Egypt. Chamomile has been used for the treatment of stomach problems, cramps, dermatitis, and minor infections. The purpose of this study was to introduce the botanical characteristics and geographical distribution, traditional uses, chemical constituents, pharmacological activities, toxicity studies and quality control studies, and lay a theoretical foundation for the rational development and utilization of chamomile. This review powered that chemical constituents include flavonoids, coumarins, volatile oils, terpenes, organic acids, polysaccharides, and others. These compounds possess anticancer, anti-infective, anti-inflammatory, antithrombotic, antioxidant, hypolipidaemic, hypoglycaemic, antihypertensive, antidepressant, neuroprotective activities, among others. Chamomile is a widely used herb in traditional medicine. It brings great economic value due to its numerous pharmacological effects and traditional uses. However, more toxicity tests should be carried out to confirm its safety. There is need for further research to provide concrete scientific evidence and validate its medicinal properties.

Antiviral Properties of Baicalin: a Concise Review.

Baicalin is one of the bioactive flavonoid glycosides isolated from the dried root of Scutellaria baicalensis Georgi, Lamiaceae, with antiviral properties. In recent years, the antiviral activity of baicalin has been widely investigated to explore its molecular mechanism of action. In this mini-review, the molecular mechanisms of action of baicalin as an antiviral agent are evaluated, which included three categories: the inhibition or stimulation of JAK/STAT, TLRs, and NF-κB pathways; up or down modulation of the expression levels of IFN, IL, SOCS1/3, PKR protein, Mx1 protein, and AP-1 protein; and inhibition of cell apoptosis caused by virus infection. In addition, clinical studies of baicalin are also discussed. This literature search suggested that baicalin can serve as a potential candidate for the development of a novel broad-spectrum antiviral drug. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43450-021-00182-1.

Salvia plebeia R. Br. polysaccharides (SPP) against RSV (respiratory syncytial virus) infection: Antiviral effect and mechanisms of action.

OBJECTIVE: To investigate the antiviral effect of Salvia plebeia R. Br. polysaccharides (SPP) against RSV and underlying mechanisms. METHODS: SPP was extracted via alcohol-precipitation method and extract was separated into various fractions using ultrafiltration method. The polysaccharide content was determined using UV-Vis. Antiviral effect of SPP and fractions was measured using MTT method and Reed-Muench method. Sixty Balb/c mice were randomly divided into 6 groups, and received either Ribavirin or SPP. Their body weight and food intake were recorded every day throughout the experiment period. The lung index inhibition ratio and pulmonary virus titer were determined followed by the histological analysis of lungs. Furthermore, time-of-addition and effective stage analysis were carried out to determine the mechanism of action. The TLR-3 and TLR-4 levels in the lungs were determined using qRT-PCR. The levels of IFN-γ, IL-2 and TNF-α in serum were determined using ELISA. RESULTS: The SPP content is 4.396%. SPP has shown a good anti-RSV effect both in vitro (TI = 123.041) and in vivo models. The antiviral activity of fractions with molecular weight ≥ 10,000 is found to possess more potent antiviral activity than other fractions. SPP inhibits the RSV proliferation and reduces the lung lesions induced by RSV. The mechanism of action involves the inhibition of TLR-3 and TLR-4 in lungs, up-regulation of IFN-γ and IL-2, and down-regulation of TNF-α in serum. It is also shown to improve the body's immune function. CONCLUSION: SPP has a potential to treat diseases caused by RSV.

Brucea javanica: A review on anticancer of its pharmacological properties and clinical researches.

BACKGROUND: The dried fruits of Brucea javanica (L.) Merr (BJ) is being widely investigated, both in lab and in clinic, to explore its potential anticancer activity and molecular mechanism involved. PURPOSE: We appraised the available literature and suggested the future research directions to improve the medicinal value of BJ. METHOD: In this review, we have summarized the scientific findings from experimental and clinical studies regarding the anticancer activity and mechanisms. RESULTS: Numerous studies have reported that BJ exerts anticancer effect on various types of cancer lines through inhibiting cell proliferation, inducing apoptosis, inhibiting migration/invasion, inducing autophagy and restraining angiogenesis. Brucea javanica triggers the generation of reactive oxygen species (ROS), release of cytochrome C, activation of mitochondrial apoptosis pathway and regulation of a series of signal pathways and proteins related to cancer. The molecular mechanism involved are inhibiting the PI3K/Akt/mTOR, NF-κB and Nrf2-Notch1 pathways; up or down modulating the levels of p53, p62, p21, Bax, and Bcl-2 respectively, and inhibiting the expression of matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). Brucea javanica's efficacy in treating cancer patients either as a main or supportive treatment is also discussed in this review. CONCLUSION: This review will serve as a comprehensive resource of BJ's potential as anticancer agent and its molecular pathways. The analysis of the literature suggests that BJ can serve as a potential candidate for the treatment of cancer.

Herba Siegesbeckiae: A review on its traditional uses, chemical constituents, pharmacological activities and clinical studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Herba Siegesbeckiae, mainly includes Sigesbeckia orientalis L, Sigesbeckiae pubescens Makino and Sigesbeckiae glabrescens Makino. Herba Siegesbeckiae, also known as 'Xi-Xian Cao' (Chinese: ), has been regarded as an important traditional Chinese medicine since Tang dynasty. The dried aerial parts of Herba Siegesbeckiae are also being used as a herbal medicine in many countries such as Japan, Korea and Vietnam. In China, Herba Siegesbeckiae has been used for the treatment of rheumatic arthralgia with aching and weakness of loins and knees, as well as numbness of limbs. AIM OF THIS REVIEW: The aim of this review was to provide critical analysis on the scientific evidence to support the traditional uses of Herba Siegesbeckiae. The information available on its in botanical characteristics, traditional uses, chemical constituents, pharmacological activities, clinical studies, toxicity and quality control was summarized to understand the current research and provided the leas for future study. MATERIALS AND METHODS: The search terms "Herba Siegesbeckiae", "Sigesbeckia orientalis", "Sigesbeckia pubscens" and "Sigesbeckia glabrescens" were used to obtain the information from electronic databases such as Web of Science, China National Knowledge Infrastructure, PubMed, Google Scholar and SciFinder Scholar and other web search instruments (Springer, Yahoo search). The information provided in this review was based on peer-reviewed papers in English and Chinese. Besides, information was also collected from ancient documents. RESULT: The studies showed that Herba Siegesbeckiae contains sesquiterpenoids, diterpenoids, flavonoids and organic acids, etc. Due to these constituents, it displayed numerous pharmacological activities, such as anti-inflammatory, antitumor, antiallergic, antioxidant, antithrombotic and antibacterial activities. In addition, it showed effects in protecting myocardial and cerebral ischemia injury. CONCLUSIONS: According to its traditional uses, chemical constituents, pharmacological activities and clinic studies, Herba Siegesbeckiae is regarded as a promising medical plant with various chemical compounds and numerous pharmacological activities. However, fewer experimental studies were focused on toxicity and quantitative study of 3 species. It suggested that further in-depth study of toxicity and quality control were critical for future evaluation of drug efficacy and safety.

A review: Natural polysaccharides from medicinal plants and microorganisms and their anti-herpetic mechanism.

The infections caused by Herpes simplex viruses (HSV-1 and -2) are seriously endangering the health of all human beings. Once infected with these two viruses, it will cause life-long latency in the host, and the continuous recurrence of the infection will seriously affect the quality of life. Moreover, infections with HSV-1 and HSV-2 have been reported to make the body susceptible to other diseases, such as Alzheimer's disease and HIV. Thus, more attention should be paid to the development of novel anti-HSV drugs. Polysaccharides obtained from medicinal plants and microorganism (both land and sea) are reported to be promising anti-herpes substances. However, their antiviral mechanisms are complex and diverse, which includes direct inhibition of virus life cycle (Adsorption, penetration, genetic material and protein synthesis) and indirectly through improving the body's immunity. And each step of the research processes from extraction to structural analysis contributes to the result in terms of antiviral activity. Therefore, The complex mechanisms involved in the treatment of Herpes simplex infections makes development of new antiviral compounds is difficult. In this paper, the mechanisms of polysaccharides in the treatment of Herpes simplex infections, the research processes of polysaccharides and their potential clinical applications were reviewed.

The physiological functions and pharmaceutical applications of inulin: A review.

Inulin (IN), a fructan-type plant polysaccharide, is widely found in nature. The major plant sources of IN include chicory, Jerusalem artichoke, dahlia etc. Studies have found that IN possessed a wide array of biological activities, e.g. as a prebiotic to improve the intestinal microbe environment, regulating blood sugar, regulating blood lipids, antioxidant, anticancer, immune regulation and so on. Currently, IN is widely used in the food and pharmaceutical industries. IN can be used as thickener, fat replacer, sweetener and water retaining agent in the food industry. IN also can be applied in the pharmaceutics as stabilizer, drug carrier, and auxiliary therapeutic agent for certain diseases such as constipation and diabetes. This paper reviews the physiological functions of IN and its applications in the field of pharmaceutics, analyzes its present research status and future research direction. This review will serve as a one-in-all resource for the researchers who are interested to work on IN.

Ixeris sonchifolia: a review of its traditional uses, chemical constituents, pharmacology and modern applications.

Ixeris sonchifolia (IS), principally its dried form, is widely used as traditional and folk medicines in some Asian countries, especially China. In this review, we summarized its traditional uses, chemical constituents, quality control measures, pharmacological activities, therapeutic evaluation, toxicity evaluation and clinical applications. 130 chemical constituents isolated from IS have been reported, including flavones, sesquiterpenes, triterpenes, phenylpropanoids, organic acids and others. They showed various pharmacological activities, such as protecting cardiocerebral vascular system, anticancer effect and antiviral etc. The quality control evaluation studies, clinical applications, other possible applications and suggestions for future research also were discussed. The aim of this review is to critically appraise the available literature and suggest directions for further development of IS to improve its medical value and use.

Salvia plebeia R. Br. : an overview about its traditional uses, chemical constituents, pharmacology and modern applications.

Salvia plebeia R. Br. (SP), has been widely used in traditional Chinese medicine (TCM). It contains a number of chemical components and reported to possess a variety of pharmacological activities. SP is distributed in many countries such as China, Korea, Japan, Afghanistan and India. SP was first described in Compendium of Materia Medica in the Ming dynasty. The aim of this review is to compile all the information reported in the literature on SP. This review covers traditional uses, including 16 TCM classics and 21 traditional prescriptions; a total of 93 compounds from SP have been reported, including flavonoids, monoterpenoids, sesquiterpenoids, diterpenoids, triterpenes, phenolic acids etc; biological actives such as antioxidant, antimicrobial, hypoglycaemic, anti-inflammatory, analgesic, sedative, antiasthmatic, antiviral, antitumour, hepatoprotective effects etc. In addition, this paper also compiled the quality control studies and clinical applications. The future prospects and the existing problems of SP were also discussed. Overall, we believe this review will be a comprehensive record of SP for researchers to refer for carrying out for further research.

Evaluation of antiviral effect and toxicity of total flavonoids extracted from Robinia pseudoacacia cv. idaho.

In this study, we aimed to evaluate the antiviral effect of total flavonoids extracted from Robinia pseudoacacia cv. idaho (RPTF) in vivo and its toxicity on rats with oral gavage. RPTF was prepared by percolation with 70% ethanol for 24 h and its antiviral effect on different kinds of viruses was evaluated in vitro by MTT staining. The long-term toxicity of RPTF on rats was evaluated through the detection of general behavior, body weight, food intake and related organ tissue sections of experimental animals. We found that RPTF produced significantly inhibitory effects on HSV-1 and EV-71 viruses with the therapeutic index TI values 113.8 and 46.2, respectively. Moreover, toxicity evaluation in vivo showed no significantly adverse effects in rats, indicating that RPTF was safe in use. In conclusion, we demonstrated that RPTF, natural compounds in the Chinese traditional medicine, could act as promising and effective antiviral therapeutics with relative safety in use.